Department of Rheumatology and Immunology, the Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of Rheumatology and Immunology, the Second Affiliated Hospital of Soochow University, Suzhou, China.
Semin Arthritis Rheum. 2024 Oct;68:152500. doi: 10.1016/j.semarthrit.2024.152500. Epub 2024 Jun 27.
Immunosuppressants, biologic agents, antifibrotic drugs, and other drugs can be used to treat autoimmune disease-associated interstitial lung disease (ILD), but the preferred treatment is uncertain. We aimed to evaluate the efficacy and safety of multiple drugs in the treatment of autoimmune disease-associated ILD.
PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for relevant randomized controlled trials (RCTs) from inception to July 2023. Primary outcomes were percentage of predicted forced vital capacity (FVC% predicted) and discontinuations for adverse events (AEs). We estimated summary mean differences (MDs) and odds ratios (ORs) using network meta-analysis with fixed effects.
The analysis is based on 15 RCTs involving 1832 patients. In terms of FVC% predicted, mycophenolate mofetil (MMF) (MD 1.27, 95 % credible interval [CrI] 0.08 to 2.43), cyclophosphamide (1.89, 0.10 to 3.68), rituximab (9.29, 2.79 to 15.80), tocilizumab (6.30, 3.27 to 9.34), nintedanib (1.71, 0.54 to 2.88), pirfenidone (2.03, 0.65 to 3.40) and nintedanib+MMF (2.43, 0.95 to 3.89) were more effective than placebo. Analysis based on a small sample size showed that riociguat also had good therapeutic potential when compared with placebo. By contrast, bosentan and pomalidomide showed no significant difference compared with placebo. Regarding discontinuations for AEs, nintedanib (OR 2.09, 95 %CrI 1.20 to 3.73) and pirfenidone (3.46, 1.31 to 10.56) were associated with higher dropout rates than placebo, and the combination therapy of nintedanib+MMF did not increase the risk of AEs compared with nintedanib monotherapy.
MMF, cyclophosphamide, rituximab, tocilizumab, nintedanib and pirfenidone are effective in the treatment of autoimmune disease-associated ILD. The efficacy of riociguat and the superiority of combination therapy need to be demonstrated in more RCTs. The tolerance of nintedanib and pirfenidone is a concern, but most of their AEs are mild and controllable.
免疫抑制剂、生物制剂、抗纤维化药物和其他药物可用于治疗自身免疫性疾病相关的间质性肺病（ILD），但首选治疗方法尚不确定。本研究旨在评估多种药物治疗自身免疫性疾病相关 ILD 的疗效和安全性。
从建库至 2023 年 7 月，检索 PubMed、Embase、Web of Science、Cochrane 中央对照试验注册库和 ClinicalTrials.gov 以获取相关随机对照试验（RCT）。主要结局指标为预计用力肺活量百分比（FVC%预计值）和因不良事件（AE）停药。我们采用固定效应网络荟萃分析来估计汇总均数差（MD）和比值比（OR）。
该分析基于 15 项 RCT，共纳入 1832 例患者。在 FVC%预计值方面，霉酚酸酯（MMF）（MD 1.27，95%可信区间[CrI] 0.08 至 2.43）、环磷酰胺（1.89，0.10 至 3.68）、利妥昔单抗（9.29，2.79 至 15.80）、托珠单抗（6.30，3.27 至 9.34）、尼达尼布（1.71，0.54 至 2.88）、吡非尼酮（2.03，0.65 至 3.40）和尼达尼布+MMF（2.43，0.95 至 3.89）的疗效优于安慰剂。基于小样本量的分析表明，利奥西呱也具有良好的治疗潜力。相比之下，波生坦和泊马度胺与安慰剂相比无显著差异。在因 AE 停药方面，尼达尼布（OR 2.09，95%CrI 1.20 至 3.73）和吡非尼酮（3.46，1.31 至 10.56）的停药率高于安慰剂，尼达尼布+MMF 联合治疗与尼达尼布单药治疗相比，AE 风险并未增加。
MMF、环磷酰胺、利妥昔单抗、托珠单抗、尼达尼布和吡非尼酮对自身免疫性疾病相关 ILD 有效。利奥西呱的疗效和联合治疗的优势需要更多 RCT 来证实。尼达尼布和吡非尼酮的耐受性令人担忧，但大多数 AE 为轻度且可控制。
